TGen Talks—Episode 69: Dr. Aleksandar Sekulic
Karie Dozer [00:00:03] I'm Kerry Dozer and this is TGen Talks. Our skin: it's our body's largest organ. Yet it's often overlooked when we think about cancer and how to prevent it. Today we dive into the world of health care, medicine, and cutting-edge research with our guest, Doctor Aleksandar Sekulic, professor in the Integrated Cancer Genomics Division at TGen and director of Dermatology and Translational Research at City of Hope Cancer Center Phenix. Dr. Sekulic’s work focuses on complex skin cancers and as both clinical physician and researcher, his work with patients helps guide his work in the lab, developing new drugs to treat various skin cancers. He's led prominent clinical trials, including those that brought the first targeted therapy and the first immunotherapy for basal cell carcinoma to approval by the FDA. Doctor Sekulic, welcome, and thanks for taking some time to be with us on the podcast.
Dr. Aleksandar Sekulic [00:01:03] Thank you for having me.
Karie Dozer [00:01:04] You're a new hire here at TGen and City of Hope. What made you choose to continue your career here with these two organizations?
Dr. Aleksandar Sekulic [00:01:11] Well, I'm new and I'm an old rehire, I guess. So I've been actually affiliated with, teaching for quite a number of years, working with Doctor Trent and the group that was focusing on the skin cancer research at the time, which is my focus in my area of interest and expertise. And that launched a series of collaborations that have persisted over the years. And I think there is a tremendous opportunity with combined, expertise of TGen in terms of research and genomics and omics in general, in partnership with clinical strength and opportunities at city of Hope and the enormous market in the area of the Valley and Arizona in general.
Karie Dozer [00:01:55] You hold a dual appointment clinician and researcher. Tell me a little bit about how you divide your time and what those two hats look like that you wear.
Dr. Aleksandar Sekulic [00:02:03] Yeah. Through throughout my entire career, I did both. And the reason is I love interactions with patients. I love medicine. And, seeing the real issues in real life of the patients brings a different, insight, different type of insight and different flavor to, any efforts to improve health. But just seeing patients is not sufficient. You know if you really want to push the envelope. You really you have to be involved on the research aspect, and that can be in various flavors. In my case, it is both in terms of clinical trials. So, developing and studying new types of treatments as well as new types of diagnostic approaches, but also looking really under the hood and looking at the mechanisms that drive the disease and asking, why is it there? What is it there that we could leverage to improve care of our patients?
Karie Dozer [00:03:01] Did you begin by wanting to wear both of those hats, and if not, which did you do first?
Dr. Aleksandar Sekulic [00:03:07] Well, I first went to medical school, and then I pursued, a graduate school in immunology and cancer biology. And the reason was seeing things that I saw in the clinic, there were many, many questions, you know, we're answering and keep answering many questions, but there's a lot more to answer. So that really was the impetus to say, you know, I really want to understand and be part of figuring out how do we do things better rather than just doing them the same way.
Karie Dozer [00:03:32] Your focus is on complex skin cancers. Before I ask you what that means. Could you divide skin cancer into a couple of categories that are most recognizable for us?
Dr. Aleksandar Sekulic [00:03:41] Absolutely. So there are many, many different types of skin cancers. But when we talk about, skin cancer in general, people will think of several. Melanoma is obviously one, probably the best known and most feared. And then we have those that are not that are more common than melanoma, but not as aggressive typically as melanoma. And that includes basal cell carcinoma and squamous cell carcinoma. When you look at these what we call non-melanoma skin cancers, there's a huge burden of disease meaning numbers of patients in the US. These are not mandatory to be reported, as new cancers. So, the estimates are somewhere on the order of 2 to 4 million new cases per year in this country. And then you have squamous cell carcinoma, which is probably around a million, maybe a little bit less than that. But again, these are estimates. We don't really have the real numbers.
Karie Dozer [00:04:39] And do those sometimes develop into melanoma or do they generally stay in their own in their own lane.
Dr. Aleksandar Sekulic [00:04:45] No. They're staying in their own lane. So squamous cell carcinoma is usually squamous cell carcinoma melanoma they don't cross. can they change their behavior. Yes. And sometimes we see that and sometimes we see that squamous or basal cell carcinoma which typically in. Vast majority of cases. If you remove them early on with simple surgery, you're done. But there are cases where they're not gone. And, sometimes that's because, we did not maybe see it remove the whole thing. But in many cases, I think it's because the actual cancer in a particular patient is different. It's more aggressive than what we normally think of as squamous or basal cell carcinoma.
Karie Dozer [00:05:26] On to complex cancers. Is that melanoma and others.
Dr. Aleksandar Sekulic [00:05:30] So when we talk about complex and particularly the language that has been used, which actually got introduced as we started studying these and doing clinical trials, we would talk about basal cell carcinoma, which is, as I mentioned, typically curable by simple surgical procedures. But when it recurs after surgery and it does not respond, it can turn into what is called locally advanced basal cell carcinoma. That disease is very different because, you can't really cure it with surgical methods, as you would the rest of the same accuracy. You could get to the next stage as well, from locally advanced to metastatic basal cell carcinoma, meaning a cancer that spreads from the skin, where it started growing to distant parts of the body. There is likely some biological difference in those cancers, but the main point is that traditionally we have not had treatments for those types of cancers. So those patients were treated with whatever the flavor of the day was in, in terms of old chemotherapies. More recently, within the last, ten, 12 years, we have done a lot of work studying new types of treatments in particularly basal cell carcinoma, leveraging genomics. And this was one of the aspects of my early involvement with region, targeting specific mutated proteins within basal focus cinema that act as a, as a switch light switch, which is stuck in the on position. And the drug that one would want to use is really targeting the switch and turning it off. And in that way, cutting off a signal that, tells the cancer cells to grow. So that's what we call targeted therapies. And that has been very successful and has been FDA approved. But even among those patients, people will progress, the cancer will progress, and patients will need other options. And that's where the next wave of therapies that we worked on, was important, which is, a set of immunotherapies, therapies that leverage your immune system and unleash the immune system and allow it to attack cancer.
Karie Dozer [00:07:45] And this is something you've been working on for quite a while.
Dr. Aleksandar Sekulic [00:07:47] Yes. So those were very rewarding. Efforts, bringing those therapies through the FDA approval and seeing, most importantly, how this can change the lives of our patients.
Karie Dozer [00:08:00] You were intimately involved in their discovery, right? Are these drugs that are very commonly used now?
Dr. Aleksandar Sekulic [00:08:06] Yes. So, in a scenario where you have a patient with locally advanced or metastatic, nominal, the most cancer, skin cancer, a particular basal cell carcinoma, we will use these targeted therapies. That's now a common thing. Luckily, these are not very common cases, but there is a need out there. And when we started this, the question was whether there is even such a thing as metastatic basal cell carcinoma. There was no recognition. Right. So I think this is really has changed the game for patients that do end up suffering from this disease.
Karie Dozer [00:08:43] Tell me about your work in the area of melanoma.
Dr. Aleksandar Sekulic [00:08:45] So I started working in melanoma years ago. And as I mentioned, that was one of the areas, of early corroborate collaboration with region. Melanoma has been a poster child for development, both of targeted therapies as well as immunotherapy. One of the significant early efforts that we've had was to say patients with melanoma were targeted. Therapies do not work. And that's about 50% of melanoma patients, advanced melanoma patients. So a.
Karie Dozer [00:09:17] Lot of patients.
Dr. Aleksandar Sekulic [00:09:18] That's a lot of patients. So in those patients we did not have other options. Immunotherapy was not on the scene yet. So in partnership with Jen and Cameron's cancer center with Doctor Trent, and Doctor Pat LaRusso in a large, large team, we had, conduct the clinical trial, which was one of the first trials to really look at the sequence of the cancer in order to say, are there any targets in this particular patient's cancer that may be amenable to drugs that we have today? So really bringing that to patients today that that was the goal the entire on the entire journey here.
Karie Dozer [00:09:57] Many of our listeners live here in Arizona. Obviously, we know the sun shines. It seems. Like every day. What do you wish that every Arizonan knew about skin cancers? If you could stand on top of Chen's building and tell everyone.
Dr. Aleksandar Sekulic [00:10:09] So I shouldn't generalize, but you almost can generalize in this case and say without sunshine there would not be skin cancer. So there's a very, very clear correlation. Sunshine or sun exposure is the most important and best characterized risk factor for development of skin cancer. Does it contribute to all skin cancers? These are the ones that we talked about. Melanoma Basil squamous cell carcinoma. Yes it does. Is it equally risky for everybody? Probably not. And I should say probably because there is risk for everybody. But if you are blond, blue eyed, fair complected, your risk is significantly higher than somebody who's very dark pigmented, has brown eyes, dark hair. And we were talking about this on the spectrum of humanity from somebody, you know, from Iceland to, somebody from, you know, Africa. So, the skin color is another component that will play into that equation. It is also important to remember that there's a different type of sun exposure that may be harmful. If you have a lot of sunburns, particularly early in life, that sets you up much more for melanoma. The risk for melanoma goes up. Risk for example, squamous cell carcinoma is just the opposite. It's cumulative exposure. It doesn't have to be high level sunburns, but it's gradual exposure day after day after day. So sun protection is really, really essential.
Karie Dozer [00:11:40] Here in Arizona, I feel like if we are outdoors at all, it's almost impossible to cover everything. Is it fair to expect us to be able to protect ourselves?
Dr. Aleksandar Sekulic [00:11:49] Yeah. And again, I would say, you know, this is all has to be adjusted to an individual, meaning somebody who has had 5 or 10 skin cancers and is light complected and very high-risk individual. The level of protection that I would recommend to somebody like that is much different than somebody who's darker and never had skin cancer. But having said that, I think we need to remember that sun protection isn't doesn't mean living in a box. It means avoid the sun when you can. So if you can pick shade versus full sun, pick the shade. If you can use clothing, sun protective clothing when it's sunny, that is a great option. And they're available now almost in grocery stores. And then you can use sunscreen when needed. Hat. Sunglasses of course. So all of those add up. It's just being wise and being consistent with it. I would say sun protection is not a decision that you make when you see the sun outside. It's an approach to your life where you go out, you're going to sun protect.
Karie Dozer [00:12:55] You're opening a new center here at city of Hope. Phenix. What will it do? What are its goals?
Dr. Aleksandar Sekulic [00:12:59] So, we are within city of Hope. Clinically, we're setting up a skin cancer program, which is going to focus on, detection, early detection and treatment of skin cancers. And the goals are to continue, really to push the envelope with new clinical trials to bring new and better treatment options for patients that need that. But it will tie into many other initiatives that we have actually had, and one of which is early cancer detection. By using DNA, being able to do so is important not only for skin cancers, but cancers in general. We know that advanced cancers kill people early. Cancers don't kill anybody. The problem is that we don't detect and treat cancers early. So prevention, early detection and then development of new therapies is really the trifecta of the goals.
Karie Dozer [00:13:55] It seems like detecting skin cancer would be far easier than detecting pancreatic cancer or another abdominal cancer. Because we wear our skin, it's visible, but it seems like melanomas are often diagnosed in people who don't get sun exposure in that particular place, right? Why is it so tricky? What is the deal?
Dr. Aleksandar Sekulic [00:14:15] Thank you for that. So there are melanomas, but then there are melanomas. The vast majority of melanomas arise on sun exposed skin and are related to sun exposure. And in fact, when we sequence the DNA of most melanomas, we can see specific changes, specific mutations in the DNA of cancer cells that tell us that this cell was or its precursor, was bombarded by ultraviolet light. We can see the signature of what led to that cancer. However, there are some melanomas that will develop in areas where you don't see the sun. For example, the bottom of your feet. Why are those dangerous? Well, the dangerous because one people do not notice them. Two. People, and sometimes even in medical community, people do not think of melanoma first. When something is there, particularly if it's not darkly pigmented. Right? Not all melanomas are dark. Numbers are dark, so that sometimes can lead to delayed detection and diagnosis. And that can complicate the treatment. As we said, the further you go along the path of development, the more challenging the treatment can be.
Karie Dozer [00:15:25] If you could divide your efforts and your outcomes based on early detection and treatment and pharmaceuticals, better drugs to treat cancers more effectively. Where would the balance lie?
Dr. Aleksandar Sekulic [00:15:37] That's a tricky question because we we're treating we are dealing with humans. And, you know, it's I think if you ask me, what is the most effective way to decrease the burden of skin cancer, I will say prevention and early detection by far, in that order. However, we know that prevention will not be, adopted to the measure that one would like. And we know that screening and, early detection is not optimal today, and we still have ways to go to get there. So we will still have this backlog of, people that will come up with skin cancer that will need treatment. So, ideally one would want to prevent all of them, but we need to work on all, on both sides of the equation.
Karie Dozer [00:16:24] If there's a most common misconception about skin cancers out there, what is it?
Dr. Aleksandar Sekulic [00:16:30] I would probably say two misconceptions. There are several, but I would highlight to one people here melanoma. And the panic settles in. We need to remember that vast majority of melanomas at this point are diagnosed early. 90 plus percent of melanomas are just removed with a simple surgical procedure in the office, and no issue after that. So that's number one. Now having melanoma early melanoma is not something that one should, rearrange their whole life around. Number two, skin cancer is luck of the draw. You know, I may get it. I may not get it, you know, and similar one is. Well, the damage has been done. Well, now, if I'm in the sun again, you know, which is incorrect, because every minute in the sun increases that chance. So even people that have a lot of sun damage, you can always get more if you allow it. So that's, I guess, another misconception. And the third misconception, these days, I think is, which is probably the best, news is that once people have advanced melanoma, for example, and now that's as I mentioned, we have, ushered those therapies into, non-melanoma skin cancer, squamous and basal. It used to be that there is really no adequate therapy for people with advanced metastatic disease, with onset of new therapies, particularly immunotherapy, that has changed dramatically. I have, been seeing patients now for 14 years that have had melanoma everywhere, and they have no melanoma.
Karie Dozer [00:18:11] Wow.
Dr. Aleksandar Sekulic [00:18:12] Right. So does everybody have that type of response? We are not there yet. But do we want to call it a cure or do we want to call it a long remission? I don't think the individual that had melanoma cares what you call it. If melanoma is gone for 14 years. Right. So I think that's another misconception. Not every advanced melanoma is a death sentence. We now have options for treatment that are very, very different than 10 or 15 years ago.
Karie Dozer [00:18:43] What's next on the horizon for options for treatment? If you could wave a wand and have three new drugs to treat three particular skin cancers, what would they be?
Dr. Aleksandar Sekulic [00:18:52] Yeah, I would say, again, you know, if I had a magic wand, I would probably, wave it in the direction of preventing it. So we don't need to treat it. But, if we're talking about, you know, melanoma, advanced melanoma that needs to be treated, and we need new therapies. If I were to show you a graph of the, new drugs approved in melanoma space, you would see an accelerated, exponential, number of new drugs that are being approved. We mentioned immunotherapy. The first wave of immunotherapies were a drug, were drugs that were, targeting what we call checkpoint inhibitors. Complex, you know, mouthful term. But basically what it says is that these drugs target points on immune cells that work like off buttons. Right. If you can use a drug to cover the off button so you can turn off the immune cell, the immune cell goes after cancer, right? But that's just the first wave of these medications, of these drugs. Newer drugs that we've been also studying recently, deploy other methods such as viruses that are re-engineered. To target the tumor cell and at the same time, in a selective way, increase the activation of immune system towards those tumor cells. So, for example, those types of treatments, either alone or in combination with these other treatments, are likely to make a significant difference in how effective we are treating more advanced cancer, skin cancers and cancers in general.
Karie Dozer [00:20:25] With this rate of discovery, why is why are cancer cells still so good at evading the newest treatments?
Dr. Aleksandar Sekulic [00:20:32] You know, when we think of cancer, we think of cancer as a case of evolution in a single body. In other words, for cancer to be a cancer. Cancer is a disease of DNA. The way every one of our cells works. Your brain cell is different than your skin cell or than your liver cell. It functions in its own lane. The reason why does is because it has very clear instructions from your DNA what to do and what to be. What happens in cancer that all of that goes out of the window. So you not only start inappropriately using things from your DNA and behaving in a way that you shouldn't, but that DNA is mutated. So the messages that the cancer center uses to behave change what that does. It allows it to grow and divide fast, but at the same time, it puts it on a trajectory of constant change, like a virus. What does that mean? Well, it means that where you had one type of cancer cell, over time you're going to have 1000 thousand million different types. So when you treat something, it may work on 900,999, but it's not going to work on that last little bit. If that last little bit survives and cancer, you know, grow despite your therapy. That's what's going to give it opportunity to rise. So that is also a beauty of the immune therapies. Because with immune therapies we are not developing, so to speak, one bullet. We are developing an army essentially that can recognize things and monitor and surveil.
Karie Dozer [00:22:13] Anything that I've missed about asking you about your goals here at city of Hope and T Gen, and what you see happening in in your discoveries, in your research and in your clinical, patients in the next ten years.
Dr. Aleksandar Sekulic [00:22:24] I think the probably the biggest thing I would highlight is that there is a tremendous opportunity here with, partnering and with city of Hope, particularly locally here, and the need for high level cancer care in Phenix or in the Valley in general, in Arizona, for that matter, is enormous. Having the presence of the two is going to allow us to really take those discoveries, not only take them from the lab into the clinic, but really jointly build a workforce that's fluent in the language on both sides and direct the work of both clinical work at city of Hope and as well as the research work at teaching, to synergize in the most effective way to really bring those therapies and those approaches, whether it's treatment or early detection to our patients. And the goal is to improve the lives of, Arizona residents.
Karie Dozer [00:23:20] What's a good time to live in Arizona? Out of the sun, hopefully at least mostly. Thanks so much for taking the time to talk about what you're doing.
Dr. Aleksandar Sekulic [00:23:27] Thank you. Thank you for having me.
Karie Dozer [00:23:29] For more on TGen’s research, go to TGen dot org slash news. The Translational Genomics Research Institute, part of city of Hope, is an Arizona based nonprofit medical research institution dedicated to conducting groundbreaking research with life changing results. You can find more of these podcasts at TGen dot org slash TGen Talks, Apple and Spotify and most podcast platforms. For TGen Talks, I'm Karie Dozer.
